中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (5): 991-993.doi: 10.4103/1673-5374.324834

• 观点:神经损伤修复保护与再生 • 上一篇    下一篇

活动依赖性的基因组结构重塑在印记细胞中促进记忆的形成和回忆

  

  • 出版日期:2022-05-15 发布日期:2021-11-08

Activity-dependent remodeling of genome architecture in engram cells facilitates memory formation and recall

Asaf Marco*   

  1. Neuro-Epigenetics Laboratory, the Robert H. Smith Faculty of Food, Environment and Agriculture, the Hebrew University of Jerusalem, Rehovol Campus, Israel
  • Online:2022-05-15 Published:2021-11-08
  • Contact: Asaf Marco, PhD, Asaf.Marco@mail.huji.ac.il.

摘要: Neural Regen Res:印记细胞相关转录因子、表观遗传调节剂和独特基因组在记忆形成中密切相关
长期记忆的形成和保存取决于神经元回路、细胞内信号级联和突触重塑的协调活动。这些基本过程发生在印迹细胞群中。当前的印迹细胞形成模型表明,一种方法可以激活一种神经元亚群,并且通过即刻早期基因的表达可以观察这些细胞亚群。在记忆巩固过程中,激活的印迹细胞会发生物理或化学变化,从而转变为更稳定和持久的状态。值得注意的是,记忆巩固过程主要发生在初始刺激停止并且印迹细胞处于休眠或静止状态之后很久。通过原始刺激来重新激活印迹细胞重排可导致记忆提取。
来自以色列希伯来大学的Asaf Marco团队首次阐明了重新激活的印迹细胞的转录特点。通过利用高分辨率显微成像工具,结合免疫组织化学和 RNA 原位杂交测定,发现谷氨酸离子型受体 AMPA 类型亚基 1 mRNA 向重新激活的印迹神经元树突轴的转运增加。这一过程与突触区室中蛋白质水平升高相结合。总之,这些突触在功能上更强大,并且在这个阶段可能会修改记忆。最近的研究称,记忆提取涉及印迹细胞状态的短暂不稳定,然后蛋白质合成以重新稳定印迹细胞。与这一假设一致,最近显示消除印迹细胞会损害恐惧记忆学习。这些数据进一步表明印迹细胞可能会根据重新暴露和/或消退而不断更新。
文章在《中国神经再生研究(英文版)》杂志2022年5 月 5期发表。

Abstract: The formation and preservation of long-term memories critically depend upon coordinated activity of neuronal circuits, intracellular signaling cascades and synaptic remodeling (Josselyn et al., 2015). These essential processes occur in specific cell populations known as  the engram ensemble (Josselyn et al., 2015). The current model for engram formation suggests that an experience activates a sub-population of neurons that can be measured by the expression of immediate early genes (IEG), such as Arc (activity regulated cytoskeleton associated protein, Arg3.1) or cFos (Fos Proto-Oncogene, AP-1 transcription factor subunit). Activated engram cells are then physically or chemically modified during memory consolidation, where labile memory is transformed into a more stable and long-lasting state. Notably, the memory consolidation process occurs predominantly long after the initial stimulus had ceased and the engram cells are in a dormant or a quiescent state. Reactivation of the engram ensemble by subsequent presentation of the original stimuli results in memory retrieval. Therefore, temporal progressions of memory formation from learning to retrieval require several waves of delayed transcriptional and translational alterations (Josselyn et al., 2015). Nonetheless, the molecular mechanisms that enable this temporal and spatial synchronization remain elusive.